Gene expression markers for crohn's disease

Abstract

The present invention relates to methods of gene expression profiling for inflammatory bowel disease pathogenesis, in which the differential expression in a test sample from a mammalian subject of one or more IBD markers relative to a control is determined, wherein the differential expression in the test sample is indicative of an IBD in the mammalian subject from which the test sample was obtained.

1 . A method of diagnosing the presence of an inflammatory bowel disease (IBD) in a mammalian subject, comprising determining a differential expression level of a nucleic acid encoding a polypeptide shown as any one of SEQ ID NOS: 5, 6, 8, 11, 12, 2, 14, 16, 18, 20, and 22 in a test sample obtained from the subject relative to the expression level of a control, wherein said differential level of expression is indicative of the presence of an IBD in the subject from which the test sample was obtained. 
     
     
         2 . The method of  claim 1 , wherein the differential level of expression is a lower level of expression for a nucleic acid encoding a polypeptide shown as any one of SEQ ID NOS: 5, 6, 8, 11, 12, 2, 14, and 16, wherein the lower level of expression is indicative of the presence of an IBD in the subject from which the test sample was obtained. 
     
     
         3 . The method of  claim 1 , wherein the differential level of expression is a higher level of expression for a nucleic acid encoding a polypeptide shown as any one of SEQ ID NOS: 18, 20, and 22, wherein the higher level of expression is indicative of the presence of an IBD in the subject from which the test sample was obtained. 
     
     
         4 . The method of  claim 1 ,  2 , or  3  wherein said mammalian subject is a human patient. 
     
     
         5 . The method of  claim 4  wherein evidence of said expression level is obtained by a method of gene expression profiling. 
     
     
         6 . The method of  claim 4  wherein said method is a PCR-based method. 
     
     
         7 . The method of  claim 5  wherein said expression levels are normalized relative to the expression levels of one or more reference genes, or their expression products. 
     
     
         8 . The method of  claim 1  comprising determining evidence of the expression levels of at least two of said genes, or their expression products. 
     
     
         9 . The method of  claim 1  comprising determining evidence of the expression levels of at least three of said genes, or their expression products. 
     
     
         10 . The method of  claim 1  comprising determining evidence of the expression levels of at least four of said genes, or their expression products. 
     
     
         11 . The method of  claim 1  comprising determining evidence of the expression levels of at least five of said genes, or their expression products. 
     
     
         12 . The method of  claim 1  further comprising the step of creating a report summarizing said IBD detection. 
     
     
         13 . The method of  claim 1  wherein said IBD is Crohn's disease. 
     
     
         14 . The method of  claim 1  wherein said test sample is from a colonic tissue biopsy. 
     
     
         15 . The method of  claim 14 , wherein said biopsy is from a tissue selected from the group consisting of the terminal ileum, the ascending colon, the descending colon, and the sigmoid colon. 
     
     
         16 . The method of  claim 14 , wherein said biopsy is from an inflamed colonic area. 
     
     
         17 . The method of  claim 14 , wherein said biopsy is from a non-inflamed colonic area. 
     
     
         18 . The method of  claim 1  wherein said determining step is indicative of a recurrence of an IBD in said mammalian subject, and wherein said mammalian subject was previously diagnosed with an IBD and treated for said previously diagnosed IBD. 
     
     
         19 . The method of  claim 18 , wherein said treatment comprised surgery. 
     
     
         20 . The method of  claim 1  wherein said determining step is indicative of a flare-up of said IBD in said mammalian subject. 
     
     
         21 . A method of treating an inflammatory bowel disorder (IBD) in a mammalian subject in need thereof, the method comprising the steps of
 (a) determining a differential expression level of a nucleic acid encoding a polypeptide shown as any one of SEQ ID NOS: 5, 6, 8, 11, 12, 2, 14, 16, and 18, in a test sample obtained from said subject relative to the expression level of a control, wherein said differential level of expression is indicative of the presence of an IBD in the subject from which the test sample was obtained; and   (b) administering to said subject an effective amount of an IBD therapeutic agent.   
     
     
         22 . The method of  claim 21 , wherein the differential level of expression is a lower level of expression for a nucleic acid encoding a polypeptide shown as any one of SEQ ID NOS: 5, 6, 8, 11, 12, 2, 14, and 16, wherein the lower level of expression is indicative of the presence of an IBD in the subject from which the test sample was obtained. 
     
     
         23 . The method of  claim 21 , wherein the differential level of expression is a higher level of expression for a nucleic acid encoding a polypeptide shown as any one of SEQ ID NOS: 18, 20, and 22, wherein the higher level of expression is indicative of the presence of an IBD in the subject from which the test sample was obtained. 
     
     
         24 . The method of  claim 21  wherein said mammalian subject is a human patient. 
     
     
         25 . The method of  claim 24  wherein evidence of said expression level is obtained by a method of gene expression profiling. 
     
     
         26 . The method of  claim 24  wherein said method is a PCR-based method. 
     
     
         27 . The method of  claim 26  wherein said expression levels are normalized relative to the expression levels of one or more reference genes, or their expression products. 
     
     
         28 . The method of  claim 21  comprising determining evidence of the expression levels of at least two of said genes, or their expression products. 
     
     
         29 . The method of  claim 21  comprising determining evidence of the expression levels of at least three of said genes, or their expression products. 
     
     
         30 . The method of  claim 21  comprising determining evidence of the expression levels of at least four of said genes, or their expression products. 
     
     
         31 . The method of  claim 21  comprising determining evidence of the expression levels of at least five of said genes, or their expression products. 
     
     
         32 . The method of  claim 21  further comprising the step of creating a report summarizing said IBD detection. 
     
     
         33 . The method of  claim 21  wherein said IBD is Crohn's disease. 
     
     
         34 . The method of  claim 21  wherein said test sample is from a colonic tissue biopsy. 
     
     
         35 . The method of  claim 34 , wherein said biopsy is from a tissue selected from the group consisting of the terminal ileum, the ascending colon, the descending colon, and the sigmoid colon. 
     
     
         36 . The method of  claim 34 , wherein said biopsy is from an inflamed colonic area. 
     
     
         37 . The method of  claim 34 , wherein said biopsy is from a non-inflamed colonic area. 
     
     
         38 . The method of  claim 21  wherein said determining step is indicative of a recurrence of an IBD in said mammalian subject, and wherein said mammalian subject was previously diagnosed with an IBD and treated for said previously diagnosed IBD. 
     
     
         39 . The method of  claim 38 , wherein said treatment comprised surgery. 
     
     
         40 . The method of  claim 21  wherein said determining step is indicative of a flare-up of said IBD in said mammalian subject. 
     
     
         41 . The method of  claim 21  wherein said IBD therapeutic agent is an aminosalicylate. 
     
     
         42 . The method of  claim 21  wherein said IBD therapeutic agent is a corticosteroid. 
     
     
         43 . The method of  claim 21  wherein said IBD therapeutic agent is an immunosuppressive agent.